Wingless modulates activator protein-1-mediated tumor invasion

doi:10.1038/s41388-018-0629-x

	Wingless modulates activator protein-1-mediated tumor invasion
	Zhang, Shiping1,2 ; Guo, Xiaowei 1; Wu, Honggui 1; Sun, Ying 1; Ma, Xianjue 1,3; Li, Jikai 1; Xu, Qian 4; Wu, Chenxi 1,5; Li, Qiwen 1; Jiang, Cizhong 1; Li, Wenzhe 1; Ho, Margaret S.2 ; Lv, Zhongwei 1; Xue, Lei 1,6
	2019-05-16
发表期刊	ONCOGENE (IF:6.9[JCR-2023],7.5[5-Year])
ISSN	0950-9232
卷号	38 期号:20 页码:3871-3885
发表状态	已发表
DOI	10.1038/s41388-018-0629-x
摘要	Metastasis begins with a subset of local tumor cells acquiring the potential to invade into surrounding tissues, and remains to be a major obstacle for cancer treatments. More than 90% of cancer patients died from tumor metastasis, instead of primary tumor growth. The canonical Wnt/beta-catenin pathway plays essential roles in promoting tumor formation, yet its function in regulating tumor metastasis and the underlying mechanisms remain controversial. Here we employed well-established Drosophila tumor models to investigate the regulating mechanism of Wingless (Wg) pathway in tumor invasion. Our results showed that Wg signaling is necessary and sufficient for cell polarity disruption-induced cell migration and molecular changes reminiscent of epithelial-mesenchymal transition (EMT). Moreover, reducing Wg signaling suppressed lgl(-/-)/Ras(V12)-induced tumor invasion, and cooperation between Arm and Ras(V12) is sufficient to induce tumor invasion. Mechanistically, we found that cell polarity disruption activates JNK signaling, which in turn upregulate wg expression through transcription factor activator protein-1 (AP-1). We identified a consensus AP-1 binding site located in the 2nd intron of wg, and confirmed that it is essential for AP-1 induced wg transcription both in vitro and in vivo. Lastly, we confirmed that the transcriptional activation of WNT by AP-1 is conserved in human cancer cells. These evidences reveal a positive role of Wnt/beta-catenin pathway in tumor invasion, and provide a conserved mechanism that connects JNK and Wnt signaling in regulating tumor progression.
收录类别	SCI ; SCIE
语种	英语
资助项目	Shanghai Committee of Science and Technology[18430711600] ; Shanghai Committee of Science and Technology[18140900400] ; Shanghai Committee of Science and Technology[09DZ2260100]
WOS研究方向	Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS类目	Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS记录号	WOS:000468035600008
出版者	NATURE PUBLISHING GROUP
WOS关键词	EPITHELIAL-MESENCHYMAL TRANSITION ; LONG-RANGE ACTION ; BETA-CATENIN ; ONCOGENIC RAS ; CELL-DEATH ; DROSOPHILA ; MIGRATION ; GROWTH ; CANCER ; PROLIFERATION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/40898
专题	生命科学与技术学院_PI研究组_何淑君组
通讯作者	Xue, Lei
作者单位	1.Tongji Univ, Shanghai Peoples Hosp 10, Shanghai Key Lab Signaling & Dis Res, Inst Intervent Vessel,Sch Life Sci & Technol, 1239 Siping Rd, Shanghai 200092, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 3.Yale Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, 295 Congress Ave, New Haven, CT 06519 USA 4.Fujian Univ Tradit Chinese Med, Inst Integrated Chinese & Western Med, 1 Qiu Yang Rd, Fuzhou 350122, Fujian, Peoples R China 5.North China Univ Sci & Technol, Coll Tradit Chinese Med, 21 Bohai Rd, Tangshan 063210, Peoples R China 6.Zhuhai Peoples Hosp, Ctr Intervent Radiol, Zhuhai 519000, Peoples R China
第一作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhang, Shiping,Guo, Xiaowei,Wu, Honggui,et al. Wingless modulates activator protein-1-mediated tumor invasion[J]. ONCOGENE,2019,38(20):3871-3885.
APA	Zhang, Shiping.,Guo, Xiaowei.,Wu, Honggui.,Sun, Ying.,Ma, Xianjue.,...&Xue, Lei.(2019).Wingless modulates activator protein-1-mediated tumor invasion.ONCOGENE,38(20),3871-3885.
MLA	Zhang, Shiping,et al."Wingless modulates activator protein-1-mediated tumor invasion".ONCOGENE 38.20(2019):3871-3885.